The immunologic characterization of leukemic and lymphoma cells has facilitated investigations designed to improve our understanding of the heterogeneity and pathophysiology of human leukemias and lymphomas. We have undertaken studies to characterize leukemic and lymphoma cell surface antigens with monoclonal antibodies produced by somatic cell hybridization techniques. These antibodies have proven useful for the definition of both the heterogeneity and lineage of leukemia and lymphoma cells and in defining their states of differentiation. The identification of unique cell surface antigens by serologic techniques has allowed for the rapid diagnosis and distinction of a variety of T, B, and myeloid cell leukemias from one another. Moreover, these unique cell surface profiles have permitted the development and an understanding of the relationship of the leukemic cell to states of normal T, B, and myeloid cell differentiation. The antibodies to leukemic cells have permitted the development of rapid assays for the classification and characterization of leukemias and lymphomas in man. More importantly, the identification of homogeneous leukemic and lymphoma phenotypes has led to the use of these reagents in both the diagnosis of individual malignancies and the selection of appropriate antibodies for the treatment of these disorders by autologous and mismatched transplantation. The demonstration that anti-CALLA (J5) was reactive with the majority of non-T cell leukemias and anti-Bl was reactive with most B-cell lymphomas has encouraged the use of these antibodies in marrow cleansing in autologous bone marrow transplantation. Long-term remissions have been obtained with a combination of bone marrow cleanup and aggressive chemotherapy. Thus, considerable progress has been made during the past year in the utilization of specific monoclonal antibodies for the diagnosis of leukemias and lymphomas and, more importantly, for the specific therapy of these diseases. (L8)